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Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules
 
Creator Datta, Sanchita
Roy, Syamal
Manna, Madhumita
 
Subject Infectious Diseases and Immunology
 
Description Background: Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly formsof disease among all neglected tropical diseases. There are no satisfactory drugs or vac-cine candidates available for this dreaded disease. Our previous studies showed promisingtherapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intra-muscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model.Methods: The T-cell proliferation level, the mRNA expression level of inducible nitric oxidesynthase (iNOS) and tumor growth factor-beta (TGF-�) genes and finally the phosphorylationlevels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) andp38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c micemodel immunized with radio-attenuated Leishmania donovani parasites through I.M. route.Results: Higher T-cell proliferation, increased iNOS level, and suppressed TGF-� level werefound in treated infected animal groups (100 and 150 Gy) in relation to untreated infectedanimals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groupswere increased when compared to untreated infected controls.Conclusion: The clearance of the parasites from treated infected groups of animals maybe mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovaniparasites. The killing of parasites was mediated by increase in nitric oxide release throughPDK1, PI3K and p38MAPK signaling pathways. A lower TGF-� expression has augmentedthe restored Th1 ambience in the 100 and 150 Gy treated animal groups proving further theefficacy of the candidate vaccine
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2205/1/BRAZILIAN_JOURNAL_OF_INFECTIOUS_DISEASES__V._19__(_1)_36%2D42;2015[93].pdf
Datta, Sanchita and Roy, Syamal and Manna, Madhumita (2015) Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules. The Brazilian Journal of Infectious Diseases, 19 (1). pp. 36-42.
 
Relation http://dx.doi.org/10.1016/j.bjid.2014.10.009
http://www.eprints.iicb.res.in/2205/